Calcitonin receptor is required for T-antigen-induced prostate carcinogenesis
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Ajay Kale1, Afaf Aldahish1 and Girish Shah1
1 Pharmacology, University of Louisiana College of Pharmacy, Monroe, LA 71201, USA
Keywords: calcitonin receptor; T-antigen; tumor growth; PTEN; prostate cancer
Received: November 26, 2019 Accepted: January 30, 2020 Published: March 03, 2020
Expression of calcitonin (CT) and its receptor (CTR) is frequently elevated in prostate cancer (PC) and activation of CT–CTR axis in non- invasive PC cells induces an invasive phenotype. However, the role of CT-CTR axis in prostate carcinogenesis has not been investigated. We employed a transgenic mouse prostate cancer model that uses long probasin promoter to target the expression of T-antigen in the prostate gland (LPB-Tag) along with CTR knock-out mice (CTRKO) to address this question. We cross-bred LPB-Tag mice with CTRKO to obtain four groups of mice. Prostates of these mice were obtained at the age of 90 days, fixed, paraffin-embedded, and used either for the extraction of RNA or for immunofluorescence. Prostate RNAs from different groups were reverse transcribed and used either for transcription profiling or for qRT-PCR. As expected, prostates of mice with LPB-Tag genotype displayed well-grown tumors with histologic features such as loss of normal morphology and nuclear atypia. WT as well as CTRKO mice displayed normal prostate morphology. Interestingly, LPB-Tag-CTRKO prostates also displayed relatively normal morphology which was indistinguishable from the WT. Microarray analysis as well as qRT-PCR suggested that CTRKO genotype reversed T-antigen-induced silencing of RB and PTEN gene expression as well as T-antigen-induced expression of several enzymes associated with lipid metabolism/ cholesterol biosynthesis, several cancer-related and androgen-regulated genes. The results for the first time identify mechanisms associated CTR-induced prostate carcinogenesis, and raise an exciting possibility of using a potent CT antagonist to attenuate progression of prostate cancer.
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